The phase I/II study to establish safety of the procedure, published December 10 in the New England Journal of Medicine, describes 10 patients with severe sickle cell disease who received intravenous transplants of blood-forming stem cells. The transplanted stem cells came from the peripheral blood of healthy related donors matched to the patients' tissue types.
Using this procedure, nine of 10 patients treated have normal red blood cells and reversal of organ damage caused by the disease.
Jonathan Powell, M.D., Ph.D., associate professor at the Johns Hopkins Kimmel Cancer Center, says the intravenous transplant approach for sickle cell disease, caused by a single mutation in the hemoglobin gene, does not replace the defective gene, but transplants blood stem cells that carry the normal gene.
Sickle cell disease, named for the "deflated" sickle-shaped appearance of red blood cells in those with the disease, hinders the cells' ability to carry oxygen throughout the body. In severe cases, it causes stroke, severe pain, and damage to multiple organs, including the lungs, kidneys and liver.
All patients in the study, ranging in age from 16 to 45, were treated at the NIH with what researchers call a non-myeloablative or "mini" transplant, along with an immune-suppressing drug called rapamycin.
Conventional transplant methods use high doses of chemotherapy to wipe out the immune system before the transplanted cells are injected, a process that has many side effects, including serious bacterial and fungal infections, which may kill some patients. In mini-transplants, lower doses of medication and radiation are used to make room for the donor's cells, the new source for healthy red blood cells in the patient.
According to Powell, side effects, including low white blood cell counts, were few and very mild compared with conventional bone marrow transplantation. But in nine of the 10, donor cells now coexist with the patients' own cells. One patient was not able to maintain the transplanted cells long term.
Minitransplants for sickle cell disease were tested in patients almost a decade ago, but were unsuccessful because the patients' immune systems rejected the transplanted cells, according to Powell, but by employing the drug rapamcyin, he says this new approach promotes the coexistence of the host and donor cells.
Powell's earlier research in mice showed that rapamycin inhibits an enzymatic pathway that suppresses the immune system and makes the host and donor cells tolerant to each other.
The NIH/Johns Hopkins team is conducting further studies on immune cells gathered from patients in their study, and looking at a combination of rapamycin with a well-known cancer drug called cyclophosphamide.
Other teams at Johns Hopkins are studying the use of half-matched donors for transplants in sickle cell patients, helping to widen the pool of potential donors for stem cell transplantation.
Funding for the study was provided by the National Institute of Diabetes, Digestive, and Kidney Diseases and the National Heart, Lung and Blood Institute at the NIH.
Study authors at the NIH include principal investigator John Tisdale, as well as Matthew Hsieh, Elizabeth Kang, Courtney Fitzhugh, M. Beth Link, Roger Kurlander, Richard Childs, and Griffin Rodgers.
Correct connections are crucial
26.06.2017 | Charité - Universitätsmedizin Berlin
One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
26.06.2017 | Life Sciences
26.06.2017 | Physics and Astronomy
26.06.2017 | Information Technology